Nanoparticles Coated with Neutrophil Membranes Can Effectively Treat Cancer Metastasis

Abstract

The dissemination, seeding, and colonization of circulating tumor cells (CTCs) serve as the root of distant metastasis. As a key step in the early stage of metastasis formation, colonization of CTCs in the (pre-)metastatic niche appears to be a valuable target. Evidence showed that inflammatory neutrophils possess both a CTC- and niche-targeting property by the intrinsic cell adhesion molecules on neutrophils. Inspired by this mechanism, we developed a nanosize neutrophil-mimicking drug delivery system (NM-NP) by coating neutrophils membranes on the surface of poly(latic-co-glycolic acid) nanoparticles (NPs). The membrane-associated protein cocktails on neutrophils membrane were mostly translocated to the surface of NM-NP via a nondisruptive approach, and the biobinding activity of neutrophils was highly preserved. Compared with uncoated NP, NM-NP exhibited enhanced cellular association in 4T1 cell models under shear flow in vitro, much higher CTC-capture efficiency in vivo, and improved homing to the premetastatic niche. Following loading with carfilzomib, a second generation of proteasome inhibitor, the NM-NP-based nanoformulation (NM-NP-CFZ) selectively depleted CTCs in the blood, prevented early metastasis and potentially inhibited the progress of already-formed metastasis. Our NP design can neutralize CTCs in the circulation and inhibit the formation of a metastatic niche.

Magnetic Mesoporous Silica Nanoparticles Cloaked by Red Blood Cell Membranes: Applications in Cancer Therapy

“…[4][5][6][7][8][9][10][11][12] Although these ligands contribute efforts to enhance the accumulation in the sites of interest, nanocarriers still suffer from passive immunological clearance and unsatisfied targeting property that lead to the decrease of the working concentration. [18,19] Sometimes,alarge number of nanoparticles adheres around the blood vessels,w hich causes blood clots. [18,19] Sometimes,alarge number of nanoparticles adheres around the blood vessels,w hich causes blood clots.…”

Artificial T Cell Mimetics to Combat Melanoma Tumor Growth

“…Systems such as RBC mimetic drug carriers facilitate the long-term circulation of these particles and efficient delivery to the tumor tissue 27,28 . Similarly, nanoparticles coated with neutrophil membrane have aided in targeting and capture of circulating tumor cells and efficiently decreasing tumor metastasis in vivo 29 . Integrating the advances in drug delivery to immunotherapy, in this study, we report an artificial T cell mimetic that composed of synthetic microparticles and conjugated immune checkpoint receptor PD-1 (PDMPs) to control tumor growth (Figure 7).…”

Engineering Cell Membrane‐Based Nanotherapeutics to Target Inflammation

“…Sci. [72] When loaded with carfilzomib, NM-NP selectively inhibited the progression of metastasis. Compared with other treatments, cell membrane-guided targeting has revealed positive results.…”

“…In these cases, inflammatory cells Adv. [72] Copyright 2017, American Chemical Society. 2019, 6, 1900605 Figure 11.…”